It is self-evident that a compound cannot be marketed succesfully if it cannot be produced economically. In addition to the cost of raw materials for making the compound, its cost of production depends upon numerous other factors including the purity required, the color, or lack thereof, demanded for the compound, the time required to make it, and of course, the amount of by-products and scrap which result. The weighting of each of the foregoing factors looms the larger with the increasing cost of the raw materials, the inflexibility of the conditions of reaction, and the exigency of the color qualifications, all of which lead to high scrap production in an unforgiving process. The tri-substitution of a trihalo-s-triazine, specifically cyanuric chloride, with a cyclic amine substituent is such a process.
The cyclic amine substituent is preferably derived from a piperidine, piperazine or piperazin-2-one, hexahydro-2HH-1,4-diazepine or hexahydro-2H-1,4-diazepin-2-one, any of which is an expensive material. Since, for economic reasons, essentially no unreacted cyanuric chloride may remain, preferably none which is not trisubstituted, or otherwise reacted to form unwanted byproducts, there is no practical alternative to using an excess of the amine, the bigger the excess, the more cyanuric chloride being tri-substituted. Except that separating and recovering the excess unreacted amine from the reaction mass is difficult and uneconomical. The result is that excess amine is discarded with other byproducts and wasted. It is this process to which this invention is directed.
The concept of structurally manipulating the architecture of multi-ringed hindered amine cyclic compounds along with the linking groups which link them to a triazine ring, has been at the forefront of the enormous effort to stabilize synthetic resinous materials against degradation by oxygen, heat and actinic radiation, particularly ultraviolet light. Among the most successful of the architectures are one or more triazine rings linked through a nitrogen atom, or a linking group containing a nitrogen atom, to a piperidine, piperazine, piperazin-2-one, hexahydro-2H-1,4-diazepine, or hexahydro-2H-1,4-diazepin-2-one ring which has multiple substituents on the ring carbon atoms. Each of the foregoing cyclic amines is referred to by the acronym "PSP", for brevity, because they are polysubstituted.
Substituents and tri-substituted triazines are disclosed in U.S. Pat. Nos. 4,190,571, 4,480,092, and 4,547,538 to Lai et al; and, U.S. Pat. No. 4,629,752 to Layer et al; all in class 524/subclass 100, the disclosures of which are incorporated by reference thereto as if fully set forth herein.
In example 3 of the '538 patent, cyanuric chloride is mono-substituted with a piperazinyl substituent (referred to as a piperazinyl-triazine or "PIP-T" for brevity) to form 2,4-dichloro-6-[1-methylpropyl[2-(3,3,5,5-tetramethyl-2-oxo-1-piperazinyl) ethyl]amino]-1,3,5-triazine (m p 93.degree.-95.degree. C.) by reacting equimolar amounts of 1-[2-(2-butylamino)ethyl]-3,3,5,5-tetramethyl-piperazin-2-one (a specific PSP referred to as PSP.sub.1) and cyanuric chloride in acetone and water, in the presence of sodium carbonate.
A second PSP.sub.1 may be added if a slight excess over 2 moles of the PSP.sub.1 are reacted with 1 mole of cyanuric chloride, but the reaction must be completed under reflux conditions to obtain more than 50% yield (lb recovered/lb theoretically produced).
Under such reflux conditions, the reaction for the substitution of a third PSP.sub.1 on the triazine ring, in aqueous solution, produces less than 50% yield. Recognizing the necessity of a high temperature to make the substitution on the third C atom of the triazine ring, the patent teaches carrying out the reaction in an inert organic solvent with a suitably high boiling point, for example toluene or xylene.
With another PSP, referred to as PSP.sub.4, example 6 of the '538 patent illustrates how easily the reaction of equimolar amounts of cyanuric chloride and 1-[2-(2-propylamino)ethyl]3,3,5,5-tetramethyl-piperazin-2-one in solution in toluene proceeds. The reaction is run at 10.degree. C., then a molar excess of 20% NaOH solution is stirred with the reaction mass overnight, to produce the mono-substituted triazine. Though the color of the product was good, the time required at low temperature is so long that it became necessary to run the reaction at higher temperature and elevated pressure. This shortened the time of reaction but increased the by-product formation and degraded the color. The product collected was 70 g (m p 118.degree.-121.degree. C.), which represents a yield of about 55.6%. Since such a yield precludes the commercial preparation of the compound, a more economic approach was required.
Then to introduce the second and third substituents, as described in example 7, the mono-substituted triazine ring was reacted with a PSP in toluene solution at about 200.degree. C. for 10 hr. Nothing is stated about the color of the product obtained, or its yield, or the amount of the mono-substituted reactant which remained unconverted.
Specifically, the PIP-T was tri-substituted PSP.sub.4, made in stages when 1 mole of cyanuric chloride was first reacted with 2 moles of the PSP.sub.4, with the addition of 2 moles of aqueous NaOH at a temperature below 35.degree. C. The mono-chloro intermediate ("MCI"), namely the triazine di-substituted with two PSP.sub.4 s, (m p 126.degree.-130.degree. C.), was formed. It is then stated that an additional (third) mole of the PSP.sub.4 is then reacted with a mole of cyanuric chloride. Since no molar excess of PSP.sub.4 is stated to have been used, the yield of product could not have been more than 90% even over a long period of time which would not be tolerable if the color of the product is to be white. The product is progressively colored with increasing temperature and longer time. The term "molar excess" is used herein relative to the trihalo-s-triazine used. Tri-substitution requires 3 moles of amine and 3 moles of base to neutralize the HCl formed; if 3.5 moles of amine are used, the molar excess of amine is 50%, and if 3.2 moles of base are used, the molar excess of base is 20%.
No conditions are stated for making the tri-substituted PIP-T, but referring to example 4 of the patent, it is seen that making a tri-substituted PIP-T in toluene, with PSP.sub.3 substituents, requires the reaction to be carried out at 200.degree. C. for 10 hr. That tri-substituted product (m p 179.degree.-180.degree. C.) was straw colored. When recrystallized from toluene, the product was off-white. At or above 200.degree. C., the evidence is that a desirably white product is not formed. There is no indication as to how much, if any, of the amine reactant was converted to the amine hydrochloride at the elevated temperature used. It will be appreciated that amine converted to the hydrochloride is unreactive and will not be a substituent.
It will also be appreciated that when there is a "color problem" even on a laboratory scale, the problem is magnified when the reaction is carried out on a commercial scale.
The problem of color is serious because stabilizer with a "color problem" is essentially unmarketable. The seriousness of the problem becomes the more economically debilitating because it has been found that in many instances, with a wide variety of PSPs which have been used to make the tri-substituted PIP-T, the color cannot be expunged even by multiple recrystallizations. This problem will be addressed in this specification, with specific regard to those PSPs which must be used in relatively large molar excess, namely about a 50% excess, relative to 1 mole of cyanuric chloride, to produce an economically acceptable yield of tri-substituted PIP-T. Despite such large excess of PSP, the tri-substituted PIP-T produced is typically "colored" because the reaction must be carried out at relatively high temperature, and typically, for more than 10 hr. The color generated may be due to a wide variety of factors, but a major one is that the combination of high temperature and long time is prone to yield difficult-to-separate by-products which are in large part responsible for poor color.
The approach to the twin problems of yield and color was determined by trying to best cope with them, rather than to find either a perfect or an all-encompassing solution, since it became evident that, for tri-substitution of cyanuric chloride, the presence of the relatively large molar excess of about 3.5:1 (moles of amine : cyanuric chloride), and a temperature in excess of 150.degree. C., preferably more than 200.degree. C., both appeared to be necessary to provide a practical, economic process. Further, it was to be expected that tri-substitution of cyanuric chloride with some amines would result in either more, or less, color than with other amines or triazines; and, that few, if any, amines would lend themselves to being recovered from the reaction mass economically, irrespective of the particular molar excess in which they were used.
The problems relating to manufacturing the trisubstituted PIP-T product economically are exacerbated by the fact that the PSP amines are soluble in water, and the reaction for making any PSP substitution, particularly the last, does not proceed satisfactorily in the aqueous phase. Moreover, excess amine in aqueous solution is so difficult to recover that, despite its high cost, it is presently more economical to discard it.
It happened that, unlike a cyclic amine (PSP), the solubility of MCI in water is low, but it was nevertheless essential that the loss of MCI in the aqueous phase be minimized. It was therefore advantageous to find that greater amounts of MCI migrated to the organic phase when the aqueous solution was both saline and highly basic, than when it is neutral (distilled water), and even more so when the solution was not hot. Stated differently, less of the required excess of amine went into solution in the aqueous phase when it was cold, saline and pH 14, than if the aqueous phase was not saline, was not basic, plain water.
Still further, because it was discovered that the reaction proceeded faster in the alkylbenzene phase, it became possible to use a phase transfer catalyst to accelerate the substitution of the PSPs, particularly the third (and last) substituent.
Finally, though one would reasonably expect the purity of the amine and triazine reactants to affect the color and yield of tri-substituted product, it was not reasonable to expect that the concentration of the base might have a large effect on both color and yield of product, particularly when the last substituent is to be substituted. Since each mole of HCl formed must be neutralized during the reaction, at least an equimolar amount of base must be used. Further, since the presence of some water facilitates the substitution of PSPs, typically, an aqueous solution of an alkali metal hydroxide, or an alkaline earth metal carbonate, is used. Because aqueous base is commercially economical to use, a large amount of water, far in excess of that required to initiate and propagate the reaction, is included in the reaction mass. Since the cyclic amine is soluble in water, one would expect to use as concentrated a base as practical, to avoid loss of amine during work-up of the reaction mass. Except that the more concentrated the base, the worse the color of the PIP-T product. The more dilute the base, the longer the time for reaction at the high temperature required to make the trisubstitution; and more difficult to recover both product and excess amine; and, the larger the reactor necessary.
Since it is critical that the recovered trisubstituted product, upon work-up or recrystallization, be desirably white, it was not obvious how to arrive at the appropriate range of requirements for the overall reaction, especially the aqueous phase. The color requirement for acceptable recrystallized product is defined by melting a small quantity of the crystals and measuring the melt color with a spectrophotometer; when expressed as melt absorptivity mL/gm.cm under nitrogen, acceptable color is defined as being less than 3.5 mL/gm.cm.
With the foregoing strictures it was decided to compartmentalize (or stage) the process steps. Such staging into first and second sequences of substitution was deemed to help control each step in a sequence more precisely, to minimize the formation of color-forming impurities in the first sequence, and in the second sequence, to manipulate the formation of the trisubstituted PIP-T product with desirable whiteness by minimizing the time of exposure to the required high temperature, yet to maximize yield, thus reactor productivity (weight of product per unit volume of reactor, per unit time).